The use of immunoglobulins as therapeutic treatment for a variety of diseases and disorders is rapidly increasing because they have shown to be safe and efficacious therapeutic agents. Approved therapeutic monoclonal antibodies for human use include Trastuzumab (antigen: 180 kD, HER2/neu), Alemtuzumab (antigen: 21-28 kD, CD52), and Rituximab (antigen: 35 kD, CD20). Additional therapeutic proteins are in various phases of clinical development for humans for a variety of diseases with the majority targeting various forms of cancer and inflammatory-related diseases.
Antibodies target an antigen through its binding of a specific epitope on an antigen by the interaction with the variable region of the antibody molecule. At the same time, the constant region of the antibody may additionally recruit other cells or molecules for example to destroy the cell or protein to which the antibody is bound or trigger further immune reactions. Certain regions of the immunoglobulin constant domain may elicit antibody-mediated cytotoxicity (ADCC), complement-mediated cytotoxicity (CDC), phagocytosis, immediate hypersensitivity, regulation of the 1 g synthesis, and antigen presenting cells.
Whereas antibodies have been studied and developed in several mammalian species such as humans and mice, they have been significantly less studied in companion animals such as canine, feline, and equine mammals. Treatments to address veterinary immune and inflammatory conditions have been borrowed from drugs developed for humans, often with imperfect results and generally consist of drugs classified as small molecules including non-steroidal anti-inflammatory agents, analgesic agents, steroidal agents, immunosuppressive agents or anti-metabolites, and chemotherapeutic agents. The arsenal of veterinary medicine is thus limited when it comes to addressing immune conditions and cancer. Additional drawback of these treatments is that they generally only address symptoms and they are associated with serious side effects as large doses have to be administered repeatedly for a long period of time with cumulative effects that often tend to be worse than the disease itself. There is a thus a need for improved and more specific treatments and biologic agents for use in animals, such as companion animals. Heterochimeric antibodies and antibodies having enhanced effector regions for use in treating companion animals are generally described in the Applicant's own international publications: US 2010/0061988A1 and US 2010/110838A2, the contents of each are incorporated herein by reference. There is still a need for highly specific antibodies which are not immunogenic in companion animals and which are effective to treat diseases characterized by over-proliferation of CD52-positive cells in companion animals.